Breast cancer treatment can damage a woman's ability to become pregnant, making the impact on fertility one of the key factors that many consider when choosing a therapy regimen. Now a study has found that breast cancer patients treated with a hormone-blocking drug in addition to chemotherapy were less likely to experience ovarian failure and more likely to have successful pregnancies.

Breast cancer and fertility: Breast cancer patients treated with a hormone-blocking medication in addition to chemotherapy were less likely to have ovarian failure and more likely to become pregnant after treatment.

Although the study on breast cancer and fertility has some limitations, it could suggest an alternative strategy for women who hope to become pregnant after breast cancer treatment, said George Somlo, M.D., a professor of breast oncology and staff physician at City of Hope. He was not involved in the study, but provided outside expert commentary in an interview with Medpage Today.

The Cleveland Clinic study, published in the New England Journal of Medicine, found that women who received goserelin – a synthetic version of a naturally occurring hormone – during chemotherapy experienced an 8 percent ovarian failure rate, compared to 22 percent among women who did not receive the drug. In addition, 21 percent of women who received goserelin became pregnant within five years post-treatment, compared to 11 percent of women in the control group during the same time frame.

Somlo elaborated on his perspective in this Q and A.

How does this study fit into what you know about goserelin (Zoladex) research and use of the durg?

Goserelin (Zoladex) is gonadotropin-release hormone (GnRH) agonist. Similar agents have been successfully used previously as part of postsurgical anti-hormone therapy to decrease the chance of disease recurrence by inducing early menopause in premenopausal younger women with hormone receptor positive primary breast cancer both in combination with chemotherapy, and with other anti-hormonal agents. GnRH agonists have also been studied previously, mostly in hormone receptor positive primary breast cancer patients for the purpose of protecting the ovaries for future pregnancies.

What are potential reasons for not using goserelin in these types of patients?

A previous trial in women with mostly hormone receptor positive breast cancer (a type of breast cancer making up about 55 to 60 percent of all primary breast cancers) suggested a protective effect on the ovary, but information on fertility was unavailable.

The just published outcome of an international trial (Prevention of Early Menopause Study) coordinated by the Southwest Oncology Group of the U.S., was initiated to address ovarian functional preservation, focusing on hormone receptor negative breast cancer patients, with the goal to assess ovarian failure at two years (defined as no menses for six months, and follicle-stimulating hormone levels in postmenopausal range) and also study survival.

While the results were quite encouraging, in the 218 enrolled really young (median age: 38) patients – with only 135 patients fully evaluable at two years – the ovarian failure rate was 8 percent (5) in the goserelin (Zoladex)-treated group and 22 percent (15) in the chemo only control group, suggesting that the majority of patients would have preserved or recovered their ovarian function, regardless of Zoladex.

There are also side effects associated with Zoladex and its sister drugs, with postmenopausal symptoms such as hot flush interfering with quality of life.

Are there any major limitations in this study? If so, what are they?

A total of 416 patients were to be enrolled with the goal to detect a 15 percent benefit in reducing ovarian failure rate in favor of the goserelin (Zoladex) plus chemotherapy vs. chemotherapy alone treatment group. The study was conducted between 2004-2011, and was conducted only in hormone receptor breast cancer patients. It closed early due to loss of funding.

The results turned out to be impressive, revealing a 20 percent difference in preservation of ovarian function favoring Zoladex, even though only 257 patients with premenopausal hormone receptor negative breast cancer were randomized to receive Zoladex and chemotherapy versus chemotherapy alone. Due to long study period and a smaller-than-planned number of patients studied, there were a lot of missing data points, and only 135 patients were fully evaluable with all data available at two years of follow-up from treatment.

While the four-year projected survival benefit of 92 percent in those treated with goserelin and chemo vs. 82 percent treated without goserelin is intriguing, this finding in particular needs confirmation in other trials.

Do you have anything you’d like to add?

Postsurgical chemo and hormonal therapies lead to either temporary or permanent ovarian failure, depriving women of the ability to become pregnant and resulting in menopausal symptoms.

The use of Zoladex allowed for 22 pregnancies and 18 babies born in contrast to 12 pregnancies and babies in the group treated without Zoladex. This study provides evidence that GnRH agonists such as Zoladex may provide an alternative strategy to egg harvesting and embryo cryopreservation (expensive methods that – while becoming more and more successful – when utilized in a rush prior to starting treatment of breast cancer, may also require the immediate availability of a partner, can delay treatment and carry a very high price tag).

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